摘要:

AbstractCerebral herniation is a leading cause of death in patients with fulminant hepatocellular failure. Classical signs of elevated intracranial pressure are often absent in these patients. A reliable noninvasive method by which the presence of cerebral edema could be determined is much needed. To assess the efficacy of computed tomography of the brain in this setting, we compared the radiographic findings to the intracranial pressure measured by an epidural monitor in patients with fulminant hepatic failure. Unfortunately, a considerable difference existed between the presence of cerebral edema diagnosed by computed tomography of the brain and elevation of the intracranial pressure. Our observations suggest that in patients with fulminant hepatic failure and advanced hepatic encephalopathy, computed tomography of the brain is of little value in detecting cerebral edema. Pressure monitoring is most important to establish the presence and guide the therapy of intracranial hypertension. (HEPATOLOGY 1991;13:209–212

ISSN:0270-9139    

DOI:10.1002/hep.1840130202

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractWe present the case of a 23‐yr‐old man who had had since birth marked and sustained unconjugated nonhemolytic hyperbilirubinemia and who had had several attacks of grand mal seizures. Analysis of serum bilirubin by diazoreactive methods showed serum levels of unconjugated bilirubin as high as 445 μmol/L that were not affected by phenobarbital administration. However, analysis of serum bile pigments by high‐pressure liquid chromatography demonstrated marked decrease of unconjugated bilirubin after phenobarbital treatment (from 432.4 μmol/L to 291.0 μmol/L) associated with slight increase of bilirubin monoconjugates and diconjugates (from 0.25 μmol/L to 0.42 μmol/L). Furthermore, in the past few years the patient had exhibited striking skin hyperextensibity and diaphragm eventration. This case confirms that alkaline methanolysis—high‐pressure liquid chromatography is the most reliable method for assessment of serum fraction bilirubin levels; that clinical parameters such as neurological signs do not unequivocally discriminate between type I and II Crigler‐Najjar disease and that response to phenobarbital treatment remains the main diagnostic tool. (HEPATOLOGY

ISSN:0270-9139    

DOI:10.1002/hep.1840130203

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractChlorpromazine (10 μmol/L) causes a marked increase in portal pressure in perfused rat liver. Simultaneously, oxygen consumption, hepatic clearance of taurocholate and bile flow are diminished. These effects are prevented by the cyclooxygenase inhibitors indomethacin (15 μmol/L), acetylsalicylate (3 mmol/L) or ibuprofen (200 μmol/L). On addition of chlorpromazine the liver releases increased amounts of prostaglandin D2; this increase does not occur in the presence of indomethacin.At higher concentrations of chlorpromazine (100 μmol/L) the inhibition of taurocholate clearance and bile flow is accompanied by only a moderate increase of portal pressure, and indomethacin is without effect. At this high concentration, substantial cell damage, as indicated by the release of lactate dehydrogenase, is present.We conclude that arachidonic acid—derived metabolites, notably prostanoids, are involved in the inhibition of bile flow and of taurocholate clearance observed at low concentrations of chlorpromazine. The data suggest that changes in the microcirculation are responsible for the impairment of the liver functions. At higher concentrations of chlorpromazine the cell toxicity of the drug becomes prominent. (HEPATOLOGY1991;13:216

ISSN:0270-9139    

DOI:10.1002/hep.1840130204

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractWe observed hepatocyte cytoskeletons in phalloidintreated rats by the quick‐freezing and deep‐etching method in three dimensions and compared them with the ultrastructural findings on conventional ultrathin sections. The numbers of microvilli in dilated bile canaliculi were decreased in the rats treated with phalloidin for 1 wk. In hepatocytes the cytoplasm around bile canaliculi could be divided into three layers, increased microfilament layer, cell organelle layer of secretory system and increased smooth surface endoplasmic reticulum layer. In the rats treated with phalloidin for 4 wk, microfilaments were extended into the cytoplasm near the nucleus in addition to the increased number of large lysosomes and microtubules. In both groups, three‐dimensional structures of microfilaments could be visualized around bile canaliculi and along cell borders by the quick‐freezing and deep‐etching method. The branching microfilaments with the diameters of 7 to 10 nm were directly attached to other filaments, cell organelles or cytoplasmic sides of cell membranes. Moreover, bundled intermediate filaments were increased around peribiliary microfilaments associated with long‐term cholestasis. It is suggested that excessive accumulation of peribiliary microfilaments disturb the secretion of bile components into bile canaliculi. The cytoskeletal reorganizations of intermediate filaments seem to alter the arrangements of various cell organelles. (HEPATOLOGY19

ISSN:0270-9139    

DOI:10.1002/hep.1840130205

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractCalmodulin, a low molecular weight Ca2 +binding protein, regulates a large number of cell activities including cell division. Previous studies from our laboratory indicated excessive accumulation of Ca2 +in hepatocytes succeeded by rapid glycogen breakdown and suppressed cell division in rats receiving CCl4after previous dietary exposure to 10 ppm chlordecone. Since calmodulin plays a major role in Ca2+‐regulated events and has been reported to be localized in mitotic apparatus during cell division, we have assessed subcellular distribution of calmodulin and estimated cytosolic phosphorylase a to indicate cytosolic free Ca2+levels in livers of rats fed 0 ppm or 10 ppm (chlordecone) in the diet for 15 days before CCl4(100 μ1/kg) administration to understand the role of Ca2+‐calmodulin in chlordecone + CCl4toxicity. Hepatotoxicity was assessed by determining serum AST and ALT succeeded by histopathological observations of liver sections. Serum aminotransferases were significantly elevated 6 hr after CCl4administration to normal rats and returned to control level by 24 hr. However, serum AST and ALT elevations were severalfold higher, and progressive increase was observed starting 4 hr after CCl4administration to chlordecone rats. Histopathological observations of liver sections for necrotic, swollen and lipid‐laden cells provided findings commensurate with the serum enzyme data. These data indicate that normal rats do recover from CCl4hepatotoxicity. However, the CCl4hepatotoxicity is progressive in chlordecone rats without recovery. In normal rats, CCl4administration resulted in a slight increase in phosphorylase a starting at 6 hr. The elevation of phosphorylase a was many‐fold higher, evident as early as 2 hr after CCl4administration and was progressive with time in livers of chlordeconepretreated rats. Hepatic cyclic AMP levels were not increased in any treatment groups but instead were slightly decreased in the chlordecone + CCl4combination treatment. This indicated that increased phosphorylase a is caused by increased cytosolic free Ca2+but not cyclic AMP and occurred before necrosis of hepatocytes. Calmodulin levels were significantly altered after CCl4administration to both normal and chlordecone‐treated rats. Calmodulin levels in nuclear fraction decreased initially succeeded by a marked elevation after 12 hr of CCl4administration. Although the cytosolic calmodulin levels were increased at all time points after CCl4administration, the mitochondrial and, to some extent, the microsomal calmodulin contents were decreased. These changes in redistribution of calmodulin in subcellular compartments might be associated with altered Ca2+levels. Based on this study and previous findings, altered Ca2+homeostasis evidently is an early event that may lead to a number of biochemical perturbations in the liver cells, ultimately leading to the progressive phase of chlordecone‐potentiated CCl4hepatotoxicity. (HEPATOLOGY1991

ISSN:0270-9139    

DOI:10.1002/hep.1840130206

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractWe have developed anin vitrosystem to study the interactions between biliary epithelium and lymphocytes using cultured human biliary epithelial cells. No class II antigens were detected by immunoperoxidase staining of the normal biliary epithelial cells, but alloactivated lymphocyte culture supernatants were able to induce class II expression. The activity of the supernatants was blocked with an anti‐γ‐interferon monoclonal antibody. In addition, recombinant human γ‐interferon alone induced the expression of class II antigens and increased the intensity of class I staining of cultured biliary epithelial cells. Biliary epithelial cell‐induced proliferation of alloreactive T lymphocytes demonstrated that the major histocompatibility complex molecules carry functional lymphocyteactivating determinants. The recognition of major histocompatibility complex determinants was confirmed by monoclonal antibody‐blocking studies and by stimulation of an alloreactive T‐cell clone. However, the biliary epithelial cells were much less potent stimulators than arterial endothelial cells tested in the same assay system. (HEPATOLOGY199

ISSN:0270-9139    

DOI:10.1002/hep.1840130207

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

Abstract[3H]glutamate, [3H]α‐ketoglutarate or [3H]aspartate was injected in physiological concentrations into antegrade (from portal to hepatic vein) or retrograde (from hepatic to portal vein) perfused rat liver, and the tissue distribution of radioactivity was studied by histoautoradiography. Independent of the direction of perfusion, radioactivity was accumulated in a small perivenous liver parenchymal cell population, which surrounded the terminal hepatic venules as a layer of about two to five cells thick. In contrast, accumulation of radioactivity in periportal hepatocytes was low and sometimes not detectable. This distribution pattern roughly resembled that described for the immunohistochemical distribution of glutamine synthetase in liver. The present histoautoradiographic findings demonstrate a predominant uptake of vascular glutamate, aspartate and ketoglutarate into a small perivenous cell population. They confirm previous label incorporation studies in the metabolically intact liver, demonstrating an almost exclusive uptake of vascular glutamate and α‐ketoglutarate into perivenous glutamine synthetase containing hepatocytes. In addition, evidence is presented suggesting that perivenous uptake of α‐ketoglutarate may be one determinant for hepatic glutamine synthesis, at least under the experimental conditions used here. (HEPATOLOGY1991;13:

ISSN:0270-9139    

DOI:10.1002/hep.1840130208

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractAir‐filled albumin microspheres, asialoorosomucoid and formaldehyde‐treated serum albumin are selectively taken up by endocytosis in rat liver Kupffer cells, parenchymal cells and endothelial cells, respectively. Intracellular transport and degradation of endocytosed material were studied by subcellular fractionation in sucrose and Nycodenz gradients after intravenous injection of the ligand. By using ligands labeled with125I‐tyramine—cellobiose, the subcellular distribution of labeled degradation products can be studied because they are trapped at the site of formation.The results show that the kinetics of intracellular transport are different in hepatic parenchymal, endothelial and Kupffer cells. In endothelial cells, the ligand is associated with two types of endosomes during the first minutes after internalization and then is transferred rapidly to the lysosomes. In parenchymal cells,125I‐tyramine‐cellobiose‐asialoorosomucoid was located in a relatively slowly sedimenting vesicle during the first minute after internalization and subsequently in denser endosomes. Degradation of125I‐tyramine‐cellobiose‐asialoorosomucoid in parenchymal cells started later than that of125I‐tyramine‐cellobiose‐formaldehyde‐treated serum albumin in endothelial cells. Furthermore, the ligand seemed to be transferred relatively slowly from endosomes to lysosomes, and most of the undegraded ligand was in the endosomes. The rate‐limiting step of proteolysis in parenchymal cells is probably the transport from endosomes to lysosomes. In Kupffer cells, most125I‐tyramine‐cellobiose‐microspheres are found as undegraded material in very dense endosomes up to 3 hr after injection. After 20 hr, most of the ligand is degraded in lysosomes distributed at a lower density than the endosomes in Nycodenz and sucrose gra

ISSN:0270-9139    

DOI:10.1002/hep.1840130209

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractWe have shown previously that ethanol‐induced defects in receptor‐mediated endocytosis of asialoorosomucoid occurred as early as 1 wk after ethanol feeding. This study was undertaken as an initial attempt to establish a possible role of defective receptormediated endocytosis in liver injury by investigating whether differences exist in the effects of ethanol on receptor‐mediated endocytosis in hepatocytes isolated from different regions of the liver. Perivenule cells, present in the distal half of the liver, are thought to be more susceptible to ethanol‐induced liver injury than are the periportal cells located in the proximal half of the liver acini. For these studies, we fed male Sprague‐Dawley rats for 7 days with liquid diets containing either ethanol (36% of calories) or isocaloric carbohydrate. Perivenule and periportal hepatocytes were then isolated using a digitonin‐collagenase perfusion method. In control animals, cells isolated from the perivenule region bound significantly more ligand than did cells from the periportal region. Amounts of ligand internalized and degraded were also greater in perivenule than in periportal cells in these animals. After ethanol feeding, cells isolated from both the perivenule and periportal regions bound significantly less ligand than their respective controls. This impairment in surface and total binding was more pronounced in perivenule than in periportal cells. Internalization and degradation of the ligand were also more adversely affected in the centrilobular region as shown by decreases of greater than 60% in perivenule cells and by only 20% to 30% in periportal cells of ethanol‐fed animals compared with controls. Receptor recycling was impaired in the perivenule region by ethanol administration as shown by receptor cycle times that were significantly prolonged in cells from the perivenule region but were relatively unchanged in periportal cells. These results indicate that ethanolinduced impairments in receptor‐mediated endocytosis are more dramatic in the perivenule region of the liver, thus suggesting a potential role of defective receptor‐mediated endocytosis in ethanol‐induced liver injury. (HEPATOL

ISSN:0270-9139    

DOI:10.1002/hep.1840130210

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractAlthough altered cytokine homeostasis has been implicated in the pathogenesis of alcoholic liver disease, the relationship between cytokines and metabolic consequences of alcoholic liver disease is unknown. We, therefore, sought to correlate circulating concentrations of tumor necrosis factor‐α, interleukin‐1 and interleukin‐6 to clinical and biochemical parameters of liver disease in chronic alcoholic patients. We used an enzyme‐linked immunosorbent assay to measure plasma tumor necrosis factor and interleukin‐1 and a bioassay to measure serum interleukin‐6 in three groups of alcoholic men as follows: (a) actively drinking alcoholic men without evidence of chronic liver disease, (b) nondrinking alcoholic men with stable cirrhosis and (c) patients with acute alcoholic hepatitis. Mean cytokine concentrations were elevated in cirrhotic patients and alcoholic hepatitis patients compared with controls and alcoholic patients without liver disease. Tumor necrosis factor‐α and interleukin‐1α concentrations remained elevated for up to 6 mo after diagnosis of alcoholic hepatitis, whereas interleukin‐6 normalized in parallel with clinical recovery. Concentrations of all three cytokines were correlated with biochemical parameters of liver injury and hepatic protein synthesis plus serum immunoglobulin concentrations. We could not demonstrate a relationship between cytokine concentrations and peripheral endotoxemia. Percentages of peripheral blood monocytes that reacted with monoclonal antibodies to CD25 (interleukin‐2 receptor) and human lymphocyte antigen‐DR were similar for alcoholic patients and controls. These data suggest that tumor necrosis factor‐α and interleukin‐1α are related to some of the metabolic consequences of both acute and chronic alcohol‐induced liver disease, whereas interleukin‐6 is related to abnormalities seen in acute liver i

ISSN:0270-9139    

DOI:10.1002/hep.1840130211

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY